DESCRIPTION: In this renewal application, the principal investigator states that recent FDA regulations are likely to increase the cost of introducing new chiral drugs and that this research program is designed to develop low cost alternatives for the synthesis of potential drug intermediates and reagents in enantiomerically pure form. A major effort is to be directed toward the use of crystallization- assisted asymmetric transformation (AT) as a way to upgrade kinetic stereoselectivity. Chiral organoboronate complexes of monofunctional and difunctional substrates are to be prepared using AT. The configuration at boron is to be controlled by crystallizing an equilibrating mixture of stereoisomers. It is noted that subsequent bond forming processes can then take place under the control of the stereogenic boron atom and that this approach will be applied to the synthesis of chiral building blocks containing quaternary carbon, starting from amino and hydroxy acids. New chiral organoboron Lewis acids are to be made for use in asymmetric transformation and also in catalysis. These reagents are to be used to activate achiral imines and sulfides for enantioselective bond forming reactions. Long range goals are said to include the conceptually related activation of carbonyl compounds and ethers. The principal investigator notes that another major part of this program involves the synthesis of chiral carbonyl compound by the asymmetric protonation of enolates. He reports that a highly effective asymmetric proton donor has been found for amide enolates and that the lead compound is a chiral aniline. He notes that efforts will be initiated to prepare simpler analogs that can be modified for increased acidity and that when this is achieved, the technique will be applied to the deracemization of esters via the enolates. It is also stated that the sequential deracemization of diol diesters will be explored as a way to achieve high enantiomer excess. A variety of other substrates are also to be studied, including derivatives of alpha-alkoxy and alpha-amino lactam, lactone, ester, and ketone enolates. Finally, the mechanistic aspects of the technique are to be probed using spectroscopic techniques.